Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

Yonghua Lei; Tianhan Hu; Xingsen Wu; Yue Wu; Qichao Bao; Lianshan Zhang; Hua Xia; Haopeng Sun; Qidong You; Xiaojin Zhang

doi:10.1021/acsmedchemlett.5b00394

Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

Yonghua Lei, Tianhan Hu, Xingsen Wu, Yue Wu, Qichao Bao, Lianshan Zhang, Hua Xia, Haopeng Sun, Qidong You, Xiaojin Zhang

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Prolyl hydroxylase domain 2 (PHD2) enzyme, a Fe^II and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.

Original language	English (US)
Pages (from-to)	1236-1240
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	6
Issue number	12
DOIs	https://doi.org/10.1021/acsmedchemlett.5b00394
State	Published - Dec 10 2015
Externally published	Yes

Keywords

FITC-labeled probe
PHD2
affinity-based
fluorescence polarization assay

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.5b00394

Cite this

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title = "Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors",

abstract = "Prolyl hydroxylase domain 2 (PHD2) enzyme, a FeII and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.",

keywords = "FITC-labeled probe, PHD2, affinity-based, fluorescence polarization assay",

author = "Yonghua Lei and Tianhan Hu and Xingsen Wu and Yue Wu and Qichao Bao and Lianshan Zhang and Hua Xia and Haopeng Sun and Qidong You and Xiaojin Zhang",

note = "Publisher Copyright: {\textcopyright} 2015 American Chemical Society.",

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doi = "10.1021/acsmedchemlett.5b00394",

language = "English (US)",

volume = "6",

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T1 - Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

AU - Lei, Yonghua

AU - Hu, Tianhan

AU - Wu, Xingsen

AU - Wu, Yue

AU - Bao, Qichao

AU - Zhang, Lianshan

AU - Xia, Hua

AU - Sun, Haopeng

AU - You, Qidong

AU - Zhang, Xiaojin

PY - 2015/12/10

Y1 - 2015/12/10

N2 - Prolyl hydroxylase domain 2 (PHD2) enzyme, a FeII and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.

AB - Prolyl hydroxylase domain 2 (PHD2) enzyme, a FeII and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.

KW - FITC-labeled probe

KW - PHD2

KW - affinity-based

KW - fluorescence polarization assay

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Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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